The Food and Drug Administration is investigating preliminary data indicating that people with the human leukocyte antigen (HLA) allele HLA-B*1051 may be at greater risk of developing Stevens-Johnson syndrome and toxic epidermal necrolysis if they receive phenytoin or fosphenytoin.
The allele is found “almost exclusively in patients with ancestry across broad areas of Asia, including Han Chinese, Filipinos, Malaysians, South Asian Indians, and Thais,” the FDA announced in a posting on the agency’s MedWatch site.
Until the FDA completes the evaluation, “health care providers should consider avoiding phenytoin and fosphenytoin as alternatives for carbamazepine in patients who test positive for HLA-B*1502.”
In December 2007, the FDA announced that people of Asian ancestry with same allele who were taking carbamazepine were at increased risk for SJS and TEN. The label now reads that testing for the allele is recommended when considering carbamazepine in a patient who fits any of the categories, and that if it is present, it should not be used “unless the benefits clearly outweigh the risks,” according to the FDA.
However, because the potential risks associated with phenytoin and fosphenytoin still are being investigated, “there is not yet enough information to recommend testing” for the allele.
The risk of serious skin reactions with the drugs appears to be highest in the first months of treatment. More than 90 percent of people who had a skin reaction with carbamazepine had it during the first months of treatment.